Milk casein is proteolytically cleaved during normal gastric digestion and cheese making to produce a peptide with current commercial value. Remarkably, the peptide has recently been shown to modulate physiological responses associated with inducing satiety and reducing appetite. Since the FDA classifies this peptide as "Generally Recognized as Safe" (GRAS), the peptide may be a compelling natural appetite suppressant with safe properties. The long-term objective of this project is to validate that the peptide is a safe inhibitor of appetite and to overcome current limitations of production. The peptide's development is limited by: . low concentrations in fluid milk, the poor taste of commercial preparations containing trace levels of undesirable peptides, . lack of some physical characteristics suitable for food formulations, and undesirable economic factors. The specific aims of this phase I study is to: 1.) Confirm that commercially prepared bovine CMP suppresses appetite in people by conducting a human satiety study, 2.) Overcome current commercial limitations in production of the peptide by transgenesis, 3.) Confirm that peptide produced in the milk of transgenic mice is biologically active in a rat model. Phase ll will be used to delineate the mechanism of action of the peptide, to identify exactly which glycosylated form of the peptide is bioactive and to develop a prototype transgenic peptide. PROPOSED COMMERCIAL APPLICATION: Successful validation of the satiety effects of the peptide and improved processing described in this project will have commercial applications in two main areas. First, considering the enormous size of appetite inhibitor markets, the market size for a safe diet suppressant would be very large. Second, market opportunities will increase for CMP as a protein source for people afflicted with PKU. Even though the number of people with PKU is relatively small, the market is considerable (approximately $50 M) because of the price of PKU foods.